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A brain MRI Study of CFS: Evidence of brainstem dysfunction & altered homeostasis

Glynis Steele

Senior Member
Messages
404
Location
Newcastle upon Tyne UK
I just found this study, and thought it might be of interest. Interestingly, I also found an article, which I have put below this one, regarding d-lactic inhibiting astrocytes. There is a study underway in Australia, taking KDM's research further, regarding CFS and d-lactic, if anyone wants details, please let me know and I will send some links.

Glynis

A brain MRI study of chronic fatigue syndrome: Evidence of brainstem dysfunction and altered homeostasis

Authors: Leighton R. Barnden, Benjamin Crouch, Richard Kwiatek, Richard Burnet, Anacleto Mernone, Steve Chryssidis, Garry Scroop, Peter Del Fante

Publication: NMR in Biomedicine

Abstract [accepted, pre-proof]

To explore brain involvement in chronic fatigue syndrome (CFS), we have extended statistical parametric mapping of brain magnetic resonance (MR) images to whole-brain voxel-based regressions against clinical scores. Using SPM5 we performed voxel-based morphometry (VBM) and analysed T1- and T2-weighted spin-echo MR signal levels in 25 CFS subjects and 25 normal controls (NC). Clinical scores included CFS fatigue duration, a score based on the 10 most common CFS symptoms, the Bell score, HADS anxiety and depression, and hemodynamic parameters from 24 hour blood pressure monitoring. We also performed group hemodynamic score interaction regressions to detect locations where MR regressions were opposite for CFS and NC, thereby indicating abnormality in the CFS group. In the midbrain, white matter volume was observed to decrease with increasing fatigue duration. For T1-weighted MR and white matter volume, group hemodynamic score interactions were detected in the brainstem (strongest in midbrain grey matter), deep prefrontal white matter, the caudal basal pons and hypothalamus. A strong correlation in CFS between brainstem grey matter volume and pulse pressure suggested impaired cerebrovascular autoregulation. We argue that at least some of these changes could arise from astrocyte dysfunction. These results are consistent with an insult to the midbrain at fatigue onset that affects multiple feedback control loops to suppress cerebral motor and cognitive activity and disrupt local CNS homeostasis, including resetting of some elements of the autonomic nervous system.



Inhibition of astrocytic energy metabolism by D-lactate exposure impairs memory.
Gibbs ME, Hertz L.

Department of Anatomy and Developmental Biology, Monash University, Clayton 3800, Australia.

Abstract
Bead discrimination learning in day-old chicken was inhibited by bilateral injection into the intermediate medial mesopallium (IMM), a homolog of the mammalian brain cortex, of the poorly metabolized enantiomer of L-lactate, D-lactate. The window of vulnerability extended from 10 min before training to 20 min after training. Unilateral injection 10 min before training inhibited only in the left IMM, whereas 10 min after training injection was only inhibitory if made into the right hemisphere. The pre-training administration caused memory loss from the earliest time tested whereas memory was maintained for another 20 min when D-lactate was injected 10 min post-training. The ability of acetate, an astrocyte-specific substrate, injected into the IMM to counteract the inhibitory effect was tested. Following D-lactate injection 10 min before training, rescue of memory immediately after training was achieved by acetate as long as aspartate, an oxaloacetate precursor, was also present. This suggests that pyruvate carboxylation is necessary for net synthesis of glutamate, which is known to occur at this time [Gibbs, M.E., Lloyd, H.G.E., Santa, T., Hertz, L., 2007. Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. J. Neurosci. Res., 85, 3326-3333]. However, acetate alone rescued memory 20 min post-training (following d-lactate injection 10 min after training), indicating that pyruvate at this time is used for energy production, consistent with memory inhibition by dinitrophenol. These findings suggest that D-lactate acts by inhibiting uptake of L-lactate into astrocytes (an extracellular effect) or metabolism of pyruvate in astrocytic mitochondria (an intracellular effect). An apparent lag phase between the administration of d-lactate and its inhibition of learning favors the latter possibility. Thus, under the present experimental conditions D-lactate acts as an astrocytic metabolic inhibitor rather than as an inhibitor of neuronal L-lactate uptake, as has occasionally been suggested. Analogously, a rare reversible neurological syndrome with memory deficits, D-lactate encephalopathy, may mainly or exclusively be due to astrocytic malfunction.
 

voner

Senior Member
Messages
592
.............and they are evidently going to continue this study - check out this info from:

http://sacfs.asn.au/news/2010/04/04_22_adelaide_brain_scanning_study.htm

//////////////

Thursday 22 April 2010

South Australian rheumatologist Dr Richard Kwiatek is heading a follow-on study comparing brain MRI in CFS versus healthy controls.

Here is a message from Dr Kwiatek about the study:

I am the principal investigator of a follow-on cross-sectional study comparing brain MRI in CFS versus healthy controls to that originally conducted by Dr Richard Burnet, the (impressive and remarkable) results of which are currently under review for publication in the Journal of the Neurological Sciences.

This follow-on study is externally funded, and I have the allotted task of attempting to recruit 25 healthy controls to match the 25 individuals with CFS.

The purpose of the follow-on study is to both confirm and extend the original findings, the nature of which I hint at by the (to be published) abstract of a poster I have had accepted for presentation at the Annual Scientific Meeting of the Australian Rheumatology Association in Melbourne in May 2010.

I hope that you will be able to appreciate that these are very novel and seemingly highly significant mechanistic findings concerning the extremely vexing disorder of CFS.

Last Saturday, at the direction of the Ethics Committee of TQEH, I had published the attached advertisement in The Advertiser.

I attach the relevant Participant Information Sheet for your information as well.

Richard Kwiatek FRACP

//////////////////////////////

I added the bold for emphasis.
 
Messages
7
all these brain / spinal studies are coming together
We also had Schutzer et al the other day, and Baranuik is coming
forget about retroviruses, I think its the brain / CNS where the answers will be found, and I think some of these guys are close
I'm optimistic
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Hi dreamboy, the issue of whether its viruses or the brain are two separate things, both deserving research. How can be treat complex viruses properly if we have no idea what they are doing to us? How can we understand the brain pathology if we ignore pathogens? It all weaves together, and all paths must be pursued until we have a cheap effective cure. Bye, Alex

ps I think the MRI results were first presented at the Bond University ME/CFS conference late last year. Nancy Klimas was there I hear.
 

August59

Daughters High School Graduation
Messages
1,617
Location
Upstate SC, USA
The Schutzer Study was all about specific proteins between CFS, post-Lyme (not sure if this correct term) and healthy controls. Can't these proteins exist due to viruses and pathogens? Which means that XMRV and\or other viruses and bacterial infections could very well be the cause of these proteins?
 

Enid

Senior Member
Messages
3,309
Location
UK
Glynis - just recalling homeostasis one of the early things to go down. Heart rate, breathing, body temperature, digestive/swallowing ability (loss of consciousness twice), whole action of the gut too. Brain stem "injury" - infection ? - It all begins to tie up. The abnormal proteins found in the spinal fluid may take us forward. I have never doubted the (whatever) moves into the brain causing injury .......um and nothing whatsoever to do with the greatest of all imaginists - the Psychos.
 
Messages
5,238
Location
Sofa, UK
all these brain / spinal studies are coming together
We also had Schutzer et al the other day, and Baranuik is coming
forget about retroviruses, I think its the brain / CNS where the answers will be found, and I think some of these guys are close
I'm optimistic

Hi Dreamboy, welcome to the forums. Optimism should be helpful. :)

However, I have to step in to disagree with your point here I'm afraid, based in particular on my interest in Alzheimer's research. All the focus on Alzheimer's in recent years has been about the build-up of amyloid proteins in the brain, and there's been great excitement about that because the mechanisms of how the disease causes short-term memory loss are becoming better understood, and some promising treatments to slow down that damage are in the pipeline. However: the most exciting study I've seen is the recent discovery of antibodies in Alzheimer's patients, and the development of an antibody test that was able to distinguish Alzheimer's patients from controls with 95% accuracy. It's early days for that research and it was a small study, but the implication is that ultimately, the damage in Alzheimer's is actually caused by some virus (the actual virus hasn't been identified yet, only the shape of the antibodies...but some of us suspect it could be XMRV or something similar).

So...my point really is that it's one thing to investigate all the details of how a disease progresses, and the complexities of how it wreaks its havoc on the human body...but it's quite another thing to find the actual cause of the disease.

There's no contradiction between the sort of brain and spinal studies you're interested in, and the theory that the cause of the disease is a retrovirus. Just as with Alzheimer's, what one is studying there is the effects of the disease...but if the cause is a virus, ultimately it's surely got to be the most important thing you can do, to identify that virus.

So far, across the whole range of ideopathic conditions, medical research has tended to focus on the downstream effects, on understanding how the pathology unfolds, on managing the conditions - and this is especially true in more recent times when it's become increasingly significant that the financial benefits of that approach dramatically exceed the benefits to be gained from actually solving the problem conclusively. But personally I don't believe the constant pessimistic line that comes out of the psychology school that "we will never find the cause" - I think that looking for the cause is crucial, and that understanding the cause will unlock the understanding of everything else about each of these diseases.

And evidence of the involvement of viruses in a wide range of ideopathic conditions continues to trickle in...MS, Diabetes, bipolar disorder, and a range of other conditions, have all been linked with viruses in recent research. My personal expectation with all of these conditions is that they will all ultimately be found to be caused by viruses, and the genetic findings merely indicate the selective susceptibility to those viruses, and the details such as the brain and spinal science are merely describing one aspect of the effects on the body of the viruses.

Anyway, if you're hoping people are going to 'forget about retroviruses' any time soon, I've got a feeling you're going to be very disappointed there... :)
 
Messages
28
all these brain / spinal studies are coming together
We also had Schutzer et al the other day, and Baranuik is coming
forget about retroviruses, I think its the brain / CNS where the answers will be found, and I think some of these guys are close
I'm optimistic
So why do you think there is such a dichotomy?
 

SilverbladeTE

Senior Member
Messages
3,043
Location
Somewhere near Glasgow, Scotland
Lyme and herpes can hide in the brain/nervous system...that's how they evade the body's immune system and are therefor, so damn nasty.
ok sure, look at the brain, it is a very important part of the disease process that is ME, but you still need to find the causative agent! ;)
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
I took part in a medium sized study being done (i think it was 60? CFS patients and 60? controls) by several of these doctors/researchers mentioned in this thread.. (Richard Kwiatek, Richard Burnet and several others, i dont know the names) which was done in conjuction with the Royal Adelaide Hospital and the Queen Elizabeth hospital back in 2007. Ive no idea when that study ended as as far as I know it was never published :( . I had been told by Richard Burnet that all the CFSers in that study showed low blood flow in certain parts of brain.

The study I was involved in with Richard Burnet and others, consisted of having to have a spect scan, MRIs, 24 hr BP and heart hoilter monitoring and other things. If anyone finds the study Im refering to, done by a few of these researchers back in 2007, please let me know as Im very interested in it as I wonder if my very abnormal BP results were disregarded in final study reports, as they were so abnormal they fell out of the automatic computer cut off ranges. The researchers werent expecting to see abnormally spiking high BP in CFS as they were expecting low BPs so hadnt set their computer parameters to that level so it would of been showing as a fault. Ive since met quite a few with CFS who have the same BP issue as I have going on.

(On taking the copy of my results I was sent out back to Richard Burnet... He agreed as one could see if one looked at the graph and range, that my BP result, it did work its way up that high and above the studies cut off point...it wasnt a fault. He said he hadnt seen anyones have such a wild flutuating range before. The only other CFS specialist I know who has paid this kind of issue any attention is the well known CFS specialist Dr Bell)
 
Messages
62
Location
Adelaide
Hello Tania, did they actually send you the results of your scans etc in the study?

I participated in this study (a follow up?) in October/November last year, but I have not heard anything since, so I am really curious as to how I may have went.

When you look at the original link on the Me/CFS Australia (SA) website, the title of the article is "Publication of original Adelaide CFS MRI study" (my bolding). I am thinking by the wording of original, that this study, that is about to be published, is their first one - perhaps the one that you were in, unless you were also in a follow up study also?
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
Dr Kwiatek been invoved in a few studies over the years, but most of them have been fibromyalgia focused.

This article still hasn't been published online yet. (wait at least another week)
 

Chris

Senior Member
Messages
845
Location
Victoria, BC
Hi, Tania--you are not alone in having high BP spikes--it was one of my primary symptoms for a couple of years. It usually followed a couple of hours after a walk--was a primary form of PEM; it could go as high as 200/100 on occasion, and was accompanied by considerable left chest pain--went to Emerg several times, no troponin, no heart attack, "go home." It would slowly resolve, but would remain somewhat elevated for a couple of days.

Interestingly, the first two occasions did reveal elevated myoglobin--I suspect the result of a viral attack on my heart? Recently, I have been taking AHCC and now a low dose of statin (10mg every second day), and this has pretty much stopped these spikes--there is now evidence that statins inhibit viral (and HIV) replication. I will post more on this (but see www.plosbiology.org, Mathieu Blanc, "Host Defence against Viral Infection ...", March 2011.

I was occasionally woken up after falling asleep and, feeling wired and weird, would take my BP and discover it was sky high... Slow meditative breathing could bring down my systolic 40 points in 15 mins sometimes. Clearly autonomic disregulation was involved.

Hope yours is normalizing--it is scary! Best, Chris